不同工艺紫雪散抗惊厥药效特点及机制研究

Anticonvulsant effect of different processes of Zixue Powder in mice and its mechanism

目的研究普通工艺、传统工艺制备紫雪散的抗惊厥作用,初步探讨其作用机制。方法采用雄性SPF级ICR小鼠,随机分为对照组,模型组,传统工艺紫雪散和普通工艺紫雪散低、中、高剂量(0.78、1.56、3.12 g·kg^(−1))组及5%苯巴比妥(0.01 mL·g^(−1))组。通过颈背部sc尼可刹米注射液诱发小鼠惊厥模型,观察各组小鼠治疗后的惊厥潜伏期、死亡潜伏期、20 min死亡率;采用比色法检测大脑皮层中钙水平;Griess reagent法检测大脑皮层总NO含量;参照试剂盒说明书检测大脑皮层中谷氨酸(Glu)、γ-氨基丁酸(GABA)含量。结果与模型组比较,苯巴比妥钠、普通和传统工艺紫雪散的中、高剂量均可显著延长小鼠的惊厥潜伏期(P<0.001);普通和传统工艺紫雪散的低、中、高剂量均可显著延长惊厥小鼠的死亡潜伏期(P<0.01、0.001);模型组小鼠死亡率为100%,苯巴比妥钠组没有小鼠死亡,普通和传统工艺紫雪散的中、高剂量组死亡率明显降低。2种工艺紫雪散的抗惊厥作用具有剂量相关性,与普通工艺高剂量比较,传统工艺紫雪散高剂量可以显著延长惊厥模型小鼠的惊厥、死亡潜伏期(P<0.05、0.01),降低惊厥致死率。与模型组比较,3.12 g·kg^(−1)传统工艺和普通工艺紫雪散、苯巴比妥钠均可以显著降低小鼠脑内钙含量(P<0.05、0.001)和总NO含量(P<0.001);与普通工艺紫雪散组比较,3.12 g·kg^(−1)传统工艺紫雪散可以显著降低惊厥小鼠脑内总NO的含量(P<0.01)。与模型组比较,传统工艺和普通工艺紫雪散3.12 g·kg^(−1)组、苯巴比妥钠组小鼠脑皮层中Glu含量显著减少(P<0.05、0.001);传统工艺紫雪散3.12 g·kg^(−1)组小鼠脑皮层中GABA含量显著增加(P<0.05)。结论传统工艺和普通工艺紫雪散均具有抗惊厥作用,并且传统工艺紫雪散的抗惊厥作用优于普通工艺紫雪散。

Objective To investigate the anticonvulsant effect of Zixue Powder and its mechanism.Methods Male SPF ICR mice were assigned to the normal group,model(nikosamide,0.75 g·kg^(−1))group,Zixue Powder traditional processes low,medium and high-dose(0.78,1.56,3.12 g·kg^(−1))group,Zixue Powder ordinary processes low-dose,medium-dose and high-dose(0.78,1.56,3.12 g·kg^(−1))groups,phenobarbital(0.01 mL·g^(−1))groups.Model mice was injected subcutaneously through the back of the neck of nikethamide.The recorded data was the convulsion latency,death latency and 20 min mortality.The contents of calcium,total nitric oxide(NO),glutamate(Glu),andγ-aminobutyric acid(GABA)in cerebral cortex were detected.Results Compared with model group,phenobarbital sodium,Zixue Powder ordinary and traditional processes of medium and high dose can significantly prolong the incubation period of convulsion mice(P<0.001).Low,medium and high doses of Zixue Powder could significantly prolong the incubation period of death in mice with convulsion(P<0.01,0.001).The mortality of mice in model group was 100%,and no mice in the phenobarbital group died.The mortality of mice in the medium and high dose groups of Zixue Powder ordinary and traditional processes was significantly reduced.The anti-convulsion effect of Zixue Powder was dose-dependent.Compared with the high dose of ordinary processes,the high dose of traditional processes could significantly prolong the incubation period of convulsion and death in mice with convulsion model(P<0.05,0.01),and reduce the mortality rate of convulsion.Compared with model group,phenobarbital sodium and of traditional and ordinary processes of 3.12 g·kg^(−1) could significantly reduce calcium content(P<0.05,0.001)and total NO content(P<0.001)in brain of mice.Compared with Zixue Powder ordinary processes group,3.12 g·kg^(−1) Zixue Powder traditional processes could significantly reduce the content of total NO in the brain of convulsive mice(P<0.01).Compared with model group,the Glu content of Zixue Powder ordinary and traditional processes of 3.12 g·kg^(−1),phenobarbital sodium group was significantly decreased(P<0.05,0.001).The content of GABA in cerebral cortex of Zixue Powder traditional processes was significantly increased(P<0.05).Conclusion Both traditional and ordinary processes of Zixue Powder have anticonvulsant effect.The anticonvulsant effect of traditional processes is better than that of ordinary processes.